Study of suppressing effect to interstitial pneumonitis by nintedanib in a novel mouse model
| Project/Area Number |
17K16055
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Respiratory organ internal medicine
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| Research Institution | Nagoya City University |
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Principal Investigator |
Miura Yoko 名古屋市立大学, 医薬学総合研究院(医学), 研究員 (60563517)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
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| Keywords | 間質性肺炎モデル / 線維化 / 間質性肺炎 / モデルマウス / UIP / NSIP / 関節リウマチ / 肺線維症 |
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| Outline of Final Research Achievements |
Idiopathic pulmonary fibrosis is pathologically classified by usual interstitial pneumonia (UIP). In this study, I established a novel chronic induced-UIP (iUIP) model. D1CC×D1BC transgenic mice was induced fibrosis by intratracheal bleomycin mixed with microbubbles followed by sonoporation. Infiltrated lymphoid cells were observed in acute phase, but not in chronic phase. A bimodal fibrotic lung disease was observed in an acute phase similar to nonspecific interstitial pneumonia (NSIP) followed by chronic fibrotic phase with honeycombing similar to UIP. Next, we examined whether nintedanib treatment attenuate fibrosis in iUIP model, D1CC×D1BC mice were oral administrated nintedanib from week 6 to 14. Nintedanib treatment reduced type I collagen accumulation and attenuated fibrosis in the lung. This iUIP mouse model could provide a useful tool to elucidate mechanisms of progression to UIP, and to evaluate therapeutic interventions including nintedanib.
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| Academic Significance and Societal Importance of the Research Achievements |
間質性肺炎の中でも特発性肺線維症 (IPF/UIP) は重篤な肺疾患であるが、その作用機序等は不明点が多い。本研究で確立した新規のIP誘導モデルは、ブレオマイシンの気管支投与法を改良した方法で、肺炎誘導後に二峰性の線維化を示した。特に後期の線維化では、UIP様の症状を呈することを明らかにした。このようなUIP様の症状を示すモデルは他になく、今後UIP発症の詳細な解析が可能となる。ニンテダニブ投与による抗線維化能も明らかになったことから、新規の抗線維化剤のスクリーニングとしても活用できると考えられる。
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Report
(4 results)
Research Products
(15 results)
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[Journal Article] Effect of H2 treatment in a mouse model of rheumatoid arthritis-associated interstitial lung disease2019
Author(s)
Terasaki Y.,Terasaki M., Kanazawa S.,Kokuho M., Urushiyama H., Kajimoto Y., Kunugi S., Maruyama M., Akimoto T., Miura Y., Igarashi T.,Ohsawa I., Shimizu A
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Journal Title
Journal of Cellular and Molecular Medicine
Volume: 23
Issue: 10
Pages: 7043-7053
DOI
Related Report
Peer Reviewed
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